Acute respiratory failure (ARF) is characterized by a sequence of diffuse alveolar injury, increased capillary permeability, edema, atelectasis, cellular infiltration, and proliferation, organization, and fibrosis. The proposed SCOR will focus the efforts of a multidisciplinary research group on many of these aspects of ARF. Interactions of neutrophils with chemotactic stimuli in the lung and the reduction of tissue injury by extravascular neutrophils will be studied. The role of alveolar collapse in either potentiating or reducing tissue injury will be investigated. Mechanisms which control lung epithelial cell proliferation following diffuse injury will be explored, particularly the possibility that such proliferation is mediated by definable growth factors. Lung connective tissue responses to lung injury will be studied, as will the activation of mechanisms for degradation of newly formed connective tissue. Two major complications of ARF and its treatment are the development of lung oxygen toxicity and bacterial infection of the lungs. Each project is the SCOR will study oxygen-induced lung injury, either as a primary agent or as a modifier of injury and tissue responses produced by other means. The role of respiratory tract infection in ARF, from acquisition of new organisms to the effects of infection on lung repair, will be studied. Each project is multidisciplinary and draws on one or more Core facilities for supporting expertise. Observations will be made with clinical material and with models of ARF in small animals and nonhuman primates. The broad range of investigator expertise, the availability of diverse animal models, and the availability of clinical material will allow the proposed SCOR to mount a comprehensive investigation of lung injury and repair in ARF.